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While mechanisms mediating these cardiometabolic side effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in <jats:styled-content style=\"fixed-case\">SGA<\/jats:styled-content>\u2010treated patients. As one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus (<jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>), we hypothesized that the <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content> is involved in <jats:styled-content style=\"fixed-case\">SGA<\/jats:styled-content>\u2010induced early cardiovascular effects in Wistar rats. We evaluated the acute effects of olanzapine and melatonin in the biological clock, paraventricular nucleus and autonomic nervous system using immunohistochemistry, invasive cardiovascular measurements, and Western blot. Olanzapine induced c\u2010Fos immunoreactivity in the <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content> followed by the paraventricular nucleus and dorsal motor nucleus of the vagus indicating a potent induction of parasympathetic tone. The involvement of a <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>\u2010parasympathetic neuronal pathway after olanzapine administration was further documented using cholera toxin\u2010B retrograde tracing and vasoactive intestinal peptide immunohistochemistry. Olanzapine\u2010induced decrease in blood pressure and heart rate confirmed this. Melatonin abolished olanzapine\u2010induced <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content> c\u2010Fos immunoreactivity, including the parasympathetic pathway and cardiovascular effects while brain areas associated with olanzapine beneficial effects including the striatum, ventral tegmental area, and nucleus accumbens remained activated. In the <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>, olanzapine phosphorylated the <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103\u03b2, a regulator of clock activity, which melatonin prevented. Bilateral lesions of the <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content> prevented the effects of olanzapine on parasympathetic activity. Collectively, results demonstrate the <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content> as a key region mediating the early effects of olanzapine on cardiovascular function and show melatonin has opposing and potentially protective effects warranting additional investigation.<\/jats:p>","DOI":"10.1111\/jpi.12402","type":"journal-article","created":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T19:52:45Z","timestamp":1487793165000},"source":"Crossref","is-referenced-by-count":17,"title":["Olanzapine\u2010induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5894-3701","authenticated-orcid":false,"given":"Francisco","family":"Romo\u2010Nava","sequence":"first","affiliation":[{"name":"Hypothalamic Integration Mechanisms Laboratory Departamento de Biolog\u00eda Celular y Fisiolog\u00eda Instituto de Investigaciones Biom\u00e9dicas Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM)  M\u00e9xico city DF M\u00e9xico"},{"name":"Departamento de Psiquiatr\u00eda y Salud Mental Facultad de Medicina UNAM  M\u00e9xico city DF M\u00e9xico"},{"name":"Division of Bipolar Disorder Research Department of Psychiatry and Behavioral Neuroscience College of Medicine University of Cincinnati  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik N.","family":"Buijs","sequence":"additional","affiliation":[{"name":"Hypothalamic Integration Mechanisms Laboratory Departamento de Biolog\u00eda Celular y Fisiolog\u00eda Instituto de Investigaciones Biom\u00e9dicas Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM)  M\u00e9xico city DF M\u00e9xico"},{"name":"Netherlands Institute for Neuroscience an Institute of the Royal Netherlands Academy of Arts and Sciences  Amsterdam BA The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Vald\u00e9s\u2010Tovar","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda Subdirecci\u00f3n de Investigaciones Cl\u00ednicas Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz  M\u00e9xico city DF M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Ben\u00edtez\u2010King","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda Subdirecci\u00f3n de Investigaciones Cl\u00ednicas Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz  M\u00e9xico city DF M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MariCarmen","family":"Basualdo","sequence":"additional","affiliation":[{"name":"Hypothalamic Integration Mechanisms Laboratory Departamento de Biolog\u00eda Celular y Fisiolog\u00eda Instituto de Investigaciones 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